The purpose of this project is to elucidate the mechanism of voltage- dependent conductance for ionic channels in lipid bilayers. The specific channels selected for experimentation are those which exhibit both voltage-dependent conductance and conductance changes corresponding to single channels. Examples are EIM, alamethicin, and hemocyanin. In oxidized cholesterol bilayers, EIM has at least two discrete conductance states - a high conductance state, whose probability of occurrence is large at or near zero membrane potential, and a low conductance state, whose probability of occurrence is large at large positive or negative potentials. We want to determine whether the the low conductance is really one state or whether the low conductance is really one state or whether there are separate state for positive and negative potentials. If there are separate states, EIM can be used as a model for inactivation in biological channels, since a large depolarization starting from a negative potential would shift channels from low conductance to high conductance. A subsequent phase of this program is to test the model of EIM activation and inactivation quantitatively by comparing the kinetics of the simulated conductance changes with rate parameters measured directly for transitions between individual pairs of conductance states.